rs8190846

Variant names:

• chr8-18221180-G-A
• rs8190846
• NM_000662.8:c.-6-862G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000662.8(NAT1):​c.-6-862G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 152,078 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.018 (49 hom., cov: 32)
• Consequence: NAT1 NM_000662.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.789
• Publications: 1 publications found

Genes affected

NAT1 (HGNC:7645): (N-acetyltransferase 1) This gene is one of two arylamine N-acetyltransferase (NAT) genes in the human genome, and is orthologous to the mouse and rat Nat2 genes. The enzyme encoded by this gene catalyzes the transfer of an acetyl group from acetyl-CoA to various arylamine and hydrazine substrates. This enzyme helps metabolize drugs and other xenobiotics, and functions in folate catabolism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BS1: Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0182 (2765/152078) while in subpopulation SAS AF = 0.0364 (175/4808). AF 95% confidence interval is 0.032. There are 49 homozygotes in GnomAd4. There are 1299 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2765 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000662.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	NM_000662.8	MANE Select	c.-6-862G>A		intron	N/A	NP_000653.3
	NAT1	NM_001160175.4		c.181-862G>A		intron	N/A	NP_001153647.1
	NAT1	NM_001160176.4		c.181-862G>A		intron	N/A	NP_001153648.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAT1	ENST00000307719.9	TSL:1 MANE Select	c.-6-862G>A		intron	N/A	ENSP00000307218.4
	NAT1	ENST00000518029.5	TSL:1	c.-6-862G>A		intron	N/A	ENSP00000428270.1
	NAT1	ENST00000519006.5	TSL:1	n.522-862G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2755 AN: 151968 Hom.: 49 Cov.: 32

Gnomad AFR AF: 0.00491

Gnomad AMI AF: 0.0811

Gnomad AMR AF: 0.0148

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.00656

Gnomad SAS AF: 0.0357

Gnomad FIN AF: 0.00881

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.0255

Gnomad OTH AF: 0.0230

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0182 AC: 2765 AN: 152078 Hom.: 49 Cov.: 32 AF XY: 0.0175 AC XY: 1299 AN XY: 74326

African (AFR) AF: 0.00499 AC: 207 AN: 41476

American (AMR) AF: 0.0148 AC: 226 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 146 AN: 3470

East Asian (EAS) AF: 0.00657 AC: 34 AN: 5172

South Asian (SAS) AF: 0.0364 AC: 175 AN: 4808

European-Finnish (FIN) AF: 0.00881 AC: 93 AN: 10562

Middle Eastern (MID) AF: 0.0856 AC: 25 AN: 292

European-Non Finnish (NFE) AF: 0.0255 AC: 1736 AN: 68014

Other (OTH) AF: 0.0233 AC: 49 AN: 2106

Alfa AF: 0.0250 Hom.: 90

Bravo AF: 0.0175

Asia WGS AF: 0.0250 AC: 85 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.35
DANN	Benign	0.48
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8190846; hg19: chr8-18078689;